Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors.

Mitotic errors generate micronuclei entrapping mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates diverse genomic rearrangements associated with human diseases. How specific repair pathways recognize and process these lesions remains poorly understood. Here we use CRISPR/Cas9 to systematically inactivate distinct DSB repair pathways and interrogate the rearrangement landscape of fragmented chromosomes. Deletion of canonical non-homologous end joining (NHEJ) components substantially reduces complex rearrangements and shifts the rearrangement landscape toward simple alterations without the characteristic patterns of chromothripsis. Following reincorporation into the nucleus, fragmented chromosomes localize within sub-nuclear micronuclei bodies (MN bodies) and undergo ligation by NHEJ within a single cell cycle. In the absence of NHEJ, chromosome fragments are rarely engaged by alternative end-joining or recombination-based mechanisms, resulting in delayed repair kinetics, persistent 53BP1-labeled MN bodies, and cell cycle arrest. Thus, we provide evidence supporting NHEJ as the exclusive DSB repair pathway generating complex rearrangements from mitotic errors.

Characterization of a conjugate between poly(N-vinyl caprolactam) and a triazine-based covalent organic framework as a potential biomaterial.

Thermoresponsive polymers (TRPs) have been explored over decades for biomedical applications, and poly(N-vinylcaprolactam) (PVCL) TRP is extensively investigated due to its low toxicity and lower critical solution temperature (LCST), close to physiological temperatures. Besides this, the utilization of covalent organic frameworks (COFs), which belong to a class of porous polymers, in bio-based applications is of great interest due to their remarkable properties. Thus, the integration of PVCL and covalent organic frameworks (COFs) as conjugate materials can lead to advanced bio-based applications; however, the need is to understand the influence of the COF on the PVCL conformation. Herein, a triazine-based COF, CC-TAPT-COF, has been synthesized and completely characterized. Later, the effect of CC-TAPT-COF on the PVCL polymer conformation was studied using various techniques. In fluorescence spectroscopy, a fluorescence quenching for PVCL in the presence of CC-TAPT-COF was observed, which indicated conformational changes. Later, results from thermal fluorescence studies and dynamic light scattering as a function of temperature showed a slight decrease in LCST value for PVCL after the addition of CC-TAPT-COF concentrations. These results showed a slight effect of CC-TAPT-COF on the PVCL conformation. Likewise, a slight decrease in the transmittance value for specific bands in infrared spectra showed a slight effect of CC-TAPT-COF on the PVCL conformation. Further, results from electron microscopy and atomic force microscopy revealed a conjugate formation between PVCL and CC-TAPT-COF due to the presence of binding interactions between them. Overall, the results from several studies showed a slight effect of CC-TAPT-COF on the PVCL during conjugate formation between PVCL and CC-TAPT-COF. This study will be beneficial for the development of COF-thermoresponsive polymer conjugates with a mixture of their unique features as advanced biomaterials.

Cognitive Impairment and Its Associated Determinants Among the Elderly Population of Telangana, India: An Analytical Prevalence Study.

INTRODUCTION: Dementia is an insidious cognitive disorder featuring a decline in cognition that is not well explained by the physiology of aging. Dementia includes a group of disorders that are distinguished by a gradual loss of both cognition and the capability to execute day-to-day functions. MATERIALS AND METHODS: We conducted a cross-sectional study among 384 elderly participants in areas surrounding the All India Institute of Medical Sciences, Bibinagar, Telangana, India. Those with more than 65 years of age were included in the study, and those suffering from serious illnesses were excluded. The Montreal Cognitive Assessment (MOCA) scale, the University of California and Los Angeles (UCLA) Loneliness Scale, and the Patient Health Questionnaire (PHQ-9) were used to assess cognitive status, loneliness, and depression, respectively, among the study participants. Logistic regression was performed to identify factors associated with cognitive impairment (CI), depression, and loneliness. RESULTS: The average MOCA score of the study participants was 14.9 ± 6.9, with 28.6% of the participants exhibiting severe CI. Nearly half of the participants (49.2%) experienced moderate to high degrees of loneliness, and 39.3% experienced moderate to severe depression. Important factors found to be associated with severe CI were illiteracy (adjusted odds ratio (AOR): 2.85, 95% CI: 1.35-4.45), urban residence (AOR: 0.18, 95% CI: 0.04-0.81), living with a spouse (AOR: 0.23, 95% CI: 0.11-0.78), not consuming alcohol (AOR: 0.35, 95% CI: 0.14-0.87), and depression (AOR: 4.49, 95% CI: 1.37-14.67). CONCLUSION: CI is a serious public health problem in India. With the increasing proportion of the elderly population in the near future, CI levels will increase, especially in countries like India. Timely interventions such as early identification through community-based screening, the inclusion of a geriatric health component in primary health care, and proper counseling will help address this problem at a grassroots level.

'Life Minus Illness = Recovery': A Phenomenological Study About Experiences and Meanings of Recovery Among Individuals with Serious Mental Illness from Southern India.

Traditional medical models have given way to recovery-oriented approaches over the years in the management of individuals with serious mental illnesses. However, very little is known about such recovery-based models in the Indian context. This qualitative study used a phenomenological approach to explore the experiences and meanings of recovery among individuals with serious mental illness in southern India. Purposive sampling with maximum variation was used to recruit participants. In-depth interviews were conducted with ten participants, using a semi-structured interview guide. Thematic analysis resulted in three themes: "The illness journey," "Life minus illness = Recovery," and "It takes a village to recover,". Illness and recovery seemed to be two sides of the same coin with the context playing an influential role in the perceptions of recovery. The term "recovery" seemed to be a misnomer giving the impression that one is expected to return to an illness free state.

Evaluation of Electrical Cardiometry to Assess Fluid Responsiveness in Patients with Acute Circulatory Failure: A Comparative Study with Transthoracic Echocardiography.

Aim: Acute circulatory failure is commonly encountered in critically ill patients, that requires fluid administration as the first line of treatment. However, only 50% of patients are fluid-responsive. Identification of fluid responders is essential to avoid the harmful effects of overzealous fluid therapy. Electrical cardiometry (EC) is a non-invasive bedside tool and has proven to be as good as transthoracic echocardiography (TTE) to track changes in cardiac output. We aimed to look for an agreement between EC and TTE for tracking changes in cardiac output in adult patients with acute circulatory failure before and after the passive leg-raising maneuver. Materials and methods: Prospective comparative study, conducted at a Tertiary Care Teaching Hospital. Results: We recruited 125 patients with acute circulatory failure and found 42.4% (53 out of 125) to be fluid-responsive. The Bland-Altman plot analysis showed a mean difference of 2.08 L/min between EC and TTE, with a precision of 3.8 L/min. The limits of agreement (defined as bias ± 1.96SD), were -1.7 L/min and 5.8 L/min, respectively. The percentage of error between EC and TTE was 56% with acceptable limits of 30%. Conclusion: The percentage error beyond the acceptable limit suggests the non-interchangeability of the two techniques. More studies with larger sample sizes are required to establish the interchangeability of EC with TTE for tracking changes in cardiac output in critically ill patients with acute circulatory failure. How to cite this article: Sharma S, Ramachandran R, Rewari V, Trikha A. Evaluation of Electrical Cardiometry to Assess Fluid Responsiveness in Patients with Acute Circulatory Failure: A Comparative Study with Transthoracic Echocardiography. Indian J Crit Care Med 2024;28(7):650-656.

Eggshell membrane as a regenerative material in alveolar bone grafting in combination with advanced platelet rich fibrin.

Abstract: The eggshell and the eggshell membrane (ESM) are significant by-products of the poultry industry and are being utilized for various valuable purposes in health care, like soft tissue healing and pain alleviation. The aim and objective of our study are to assess the effect of the eggshell membrane on alveolar bone regeneration after tooth extraction. A total of 40 extraction sockets (bilateral) among 20 patients were assessed clinically for healing, and radiographic parameters of bone density and socket volume were assessed on CBCT at baseline, 3 months, and 6 months. Advanced platelet-rich fibrin was created from 5 ml of autologous blood from the patient and centrifuged for 15 minutes at 1500 RPM/168 RCF. The commercially available powdered form of egg shell membrane was used in the study. Based on the randomized allotment (coin-flip), A-PRF alone or A-PRF mixed with eggshell membrane was placed inside the extraction socket and was stabilized using 3-0 silk sutures. It was ob-served that wound healing was uneventful in all 20 patients. No evidence of dry sockets or allergic reactions was noted in any patient. Statistical analysis was done using the un-paired t-test and Mann-Whitney U test with SPSS version 20.0. P<0.05 was considered significant. On comparison of the mean bone density at baseline, 3 months, and 6 months, the socket density in the eggshell with the PRF group was higher compared to the control group. To conclude, eggshell membrane has good regenerative properties and excellent osteogenic capacity; therefore, it could be a useful graft due to its low cost, abundant availability, and simple application.

Role of Clinical Pharmacology in Diversity and Inclusion in Global Drug Development: Current Practices and Industry Perspectives: White Paper.

The 2022 United States Food and Drug Administration (US FDA) draft guidance on diversity plan (DP), which will be implemented through the Diversity Action Plans by December 2025, under the 21st Century Cures Act, marks a pivotal effort by the FDA to ensure that registrational studies adequately reflect the target patient populations based on diversity in demographics and baseline characteristics. This white paper represents the culminated efforts of the International Consortium of Quality and Innovation (IQ) Diversity and Inclusion (D&I) Working Group (WG) to assess the implementation of the draft FDA guidance by members of the IQ consortium in the discipline of clinical pharmacology (CP). This article describes current practices in the industry and emphasizes the tools and techniques of quantitative pharmacology that can be applied to support the inclusion of a diverse population during global drug development, to support diversity and inclusion of underrepresented patient populations, in multiregional clinical trials (MRCTs). It outlines strategic and technical recommendations to integrate demographics, including age, sex/gender, race/ethnicity, and comorbidities, in multiregional phase III registrational studies, through the application of quantitative pharmacology. Finally, this article discusses the challenges faced during global drug development, which may otherwise limit the enrollment of a broader, potentially diverse population in registrational trials. Based on the outcomes of the IQ survey that provided the current awareness of diversity planning, it is envisioned that in the future, industry efforts in the inclusion of previously underrepresented populations during global drug development will culminate in drug labels that apply to the intended patient populations at the time of new drug application or biologics license application rather than through post-marketing requirements.

Deficiency of m 6 A RNA methylation promotes ZBP1-mediated cell death.

m 6 A RNA methylation suppresses the immunostimulatory potential of endogenous RNA. Deficiency of m 6 A provokes inflammatory responses and cell death, but the underlying mechanisms remain elusive. Here we showed that the noncoding RNA 7SK gains immunostimulatory potential upon m 6 A depletion and subsequently activates the RIG-I/MAVS axis to spark interferon (IFN) signaling cascades. Concomitant excess of IFN and m 6 A deficiency synergistically facilitate the formation of RNA G-quadruplexes (rG4) to promote ZBP1-mediated necroptotic cell death. Collectively, our findings delineate a hitherto uncharacterized mechanism that links m 6 A dysregulation with ZBP1 activity in triggering inflammatory cell death.

Enhancing kernel oil and tailoring fatty acid composition by genomics-assisted selection for dgat1-2 and fatb genes in multi-nutrient-rich maize: new avenue for food, feed and bioenergy.

Enhancing maize kernel oil is vital for improving the bioavailability of fat-soluble vitamins. Here, we combined favourable alleles of dgat1-2 and fatb into parental lines of four multi-nutrient-rich maize hybrids (APTQH1, APTQH4, APTQH5 and APTQH7) using marker-assisted selection (MAS). Parental lines possessed favourable alleles of crtRB1, lcyE, vte4 and opaque2 genes. Gene-specific markers enabled successful foreground selection in BC1F1, BC2F1 and BC2F2, while background selection using genome-wide microsatellite markers (127-132) achieved 93% recurrent parent genome recovery. Resulting inbreds exhibited significantly higher oil (6.93%) and oleic acid (OA, 40.49%) and lower palmitic acid (PA, 14.23%) compared to original inbreds with elevated provitamin A (11.77 ppm), vitamin E (16.01 ppm), lysine (0.331%) and tryptophan (0.085%). Oil content significantly increased from 4.80% in original hybrids to 6.73% in reconstituted hybrids, making them high-oil maize hybrids. These hybrids displayed 35.70% increment in oil content and 51.56% increase in OA with 36.32% reduction in PA compared to original hybrids, while maintaining higher provitamin A (two-fold), vitamin E (nine-fold), lysine (two-fold) and tryptophan (two-fold) compared to normal hybrids. Lipid health indices showed improved atherogenicity, thrombogenicity, cholesterolaemic, oxidability, peroxidizability and nutritive values in MAS-derived genotypes over original versions. Besides, the MAS-derived inbreds and hybrids exhibited comparable grain yield and phenotypic characteristics to the original versions. The maize hybrids developed in the study possessed high-yielding ability with high kernel oil and OA, low PA, better fatty acid health and nutritional properties, higher multi-vitamins and balanced amino acids, which hold immense significance to address malnutrition and rising demand for oil sustainably in a fast-track manner.

Bridging School and Practice? Barriers to the Integration of 'Boundary Objects' for Learning and Assessment in Clinical Nursing Education.

Introduction: In clinical health professions education, portfolios, assignments and assessment standards are used to enhance learning. When these tools fulfill a bridging function between school and practice, they can be considered 'boundary objects'. In the clinical setting, these tools may be experienced as time-consuming and lacking value. This study aimed to investigate the barriers to the integration of boundary objects for learning and assessment from a Cultural-Historical Activity Theory (CHAT) perspective in clinical nursing education. Methods: Nineteen interviews and five observations were conducted with team leads, clinical educators, supervisors, students, and teachers to obtain insight into intentions and use of boundary objects for learning and assessment. Boundary objects (assessment standards, assignments, feedback/reflection/patient care/development plan templates) were collected. The data collection and thematic analysis were guided by CHAT. Results: Barriers to the integration of boundary objects included: a) conflicting requirements in clinical competency monitoring and assessment, b) different application of analytical skills, and c) incomplete integration of boundary objects for self-regulated learning into supervision practice. These barriers were amplified by the simultaneous use of boundary objects for learning and assessment. Underlying contradictions included different objectives between school and practice, and tensions between the distribution of labor in the clinical setting and school's rules. Discussion: School and practice have both convergent and divergent priorities around students' clinical learning. Boundary objects can promote continuity in learning and increase students' understanding of clinical practice. However, effective integration requires for flexible rules that allow for collaborative learning around patient care.

Osseous Metaplasia of the Endometrium: A Rare Pathological Entity.

Osseous metaplasia of the endometrium is a rare and intriguing pathological condition characterized by the presence of bony tissue within the endometrial cavity. This phenomenon can have significant clinical implications, particularly in the context of infertility. The etiology of osseous metaplasia remains unclear, although various hypotheses have been proposed, including chronic inflammation, dystrophic calcification, and residual embryonic tissue. Clinically, patients may present with secondary infertility, abnormal uterine bleeding, or pelvic pain. Diagnosis can be made based on ultrasonography and histopathological analysis of the endometrial tissue. Treatment typically involves the removal of the osseous tissue via hysteroscopy, which can lead to the restoration of normal endometrial function and potentially resolve infertility. Further research is needed to elucidate the etiological factors and optimize treatment protocols.

Public health audit of vaccine cold chain management in general practice and community pharmacy in Western Australia.

OBJECTIVE: To support immunisation providers through a cold chain management audit. METHODS: An electronic audit survey using the National Vaccine Storage Guidelines as a gold standard was developed for general practice (GP) and community pharmacy. It included automated feedback, with individualised support from a clinical nurse specialist as required. Responses were analysed to determine the proportion of providers meeting criteria in four categories: procedures, refrigerators and equipment, temperature monitoring and emergency storage. RESULTS: Of 818 providers invited, 420 GPs (89.6%) and 276 pharmacies (82%) responded. Over 70% met all procedural and emergency storage criteria. Although most providers (98.1% GPs, 97.0% pharmacies) used a data logger, the proportion measuring at 5-minute intervals, reviewing data logger printouts weekly and manually recording minimum and maximum temperatures was lower. In total, 58% of providers required follow-up by the clinical nurse specialist, most regarding the need for equipment. CONCLUSION: An electronic audit enabled public health to engage with a large number of immunisation providers. Most reported high compliance with the national guidelines although opportunities for education were identified and actioned. IMPLICATIONS FOR PUBLIC HEALTH: Electronic solutions can support public health units to engage with providers to ensure vaccines remain effective and wastage is limited.

Preparation, characterization and antioxidant and anticancerous potential of Quercetin loaded ß-glucan particles derived from mushroom and yeast.

ß-glucans are polysaccharides found in the cell walls of various fungi, bacteria and cereals. ß-glucan have been found to show various kinds of anti-inflammatory, antimicrobial, antidiabetic antioxidant and anticancerous activities. In the present study, we have isolated ß-glucan from the baker's yeast Saccharomyces cerevisiae and white button mushroom Agaricus bisporus and tested their antioxidant potential and anticancerous activity against prostate cancer cell line PC3. Particles were characterized with zeta sizer and further with FTIR that confirmed that the isolated particles are ß-glucan and alginate sealing made slow and sustained release of the Quercetin from the ß-glucan particles. Morphological analysis of the hollow and Quercetin loaded ß-glucan was performed with the SEM analysis and stability was analyzed with TGA and DSC analysis that showed the higher stability of the alginate sealed particles. Assessments of the antioxidant potential showed that Quercetin loaded particles were having higher antioxidant activity than hollow ß-glucan particles. Cell viability of the PC3 cells was examined with MTT assay and it was found that Quercetin loaded alginate sealed Agaricus bisporus derived ß-glucan particles were having lowest IC50. Further ROS generation was found to increase in a dose dependent manner. Apoptosis detection was carried out with Propidium iodide and AO/EtBr staining dye which showed significant death in the cells treated with higher concentration of the particles. Study showed that particles derived from both of the sources were having efficient anticancer activity and showing a dose dependent increase in cell death in PC3 cells upon treatment.

Non-invasive hepatic fat quantification: Can multi-echo Dixon help?

Objective: To evaluate the diagnostic accuracy of multi-echo Dixon magnetic resonance imaging (MRI) in hepatic fat quantification, in comparison with that of magnetic resonance spectroscopy (MRS), on 3.0-T MRI. Materials and Methods: Fifty-five adults with no known liver disease underwent MRI in a 3.0-T scanner for determination of the hepatic fat fraction, with two techniques: multi-echo Dixon, in a manually drawn region of interest (ROI) and in the entire liver parenchyma (automated segmentation); and MRS. The diagnostic accuracy and cutoff value for multi-echo Dixon were determined, with MRS being used as the reference standard. Results: The mean fat fraction obtained by multi-echo Dixon in the manually drawn ROI and in the entire liver was 5.2 ± 5.8% and 6.6 ± 5.2%, respectively, whereas the mean hepatic fat fraction obtained by MRS was 5.7 ± 6.4%. A very strong positive correlation and good agreement were observed between MRS and multi-echo Dixon, for the ROI (r = 0.988, r2 = 0.978, p < 0.001) and for the entire liver parenchyma (r = 0.960, r2 = 0.922, p < 0.001). A moderate positive correlation was observed between the hepatic fat fraction and body mass index of the participants, regardless of the fat estimation technique employed. Conclusion: For hepatic fat quantification, multi-echo Dixon MRI demonstrated a very strong positive correlation and good agreement with MRS (often considered the gold-standard noninvasive technique). Because multi-echo Dixon MRI is more readily available than is MRS, it can be used as a rapid tool for hepatic fat quantification, especially when the hepatic fat distribution is not homogeneous.

Objetivo: Avaliar a acurácia diagnóstica da técnica multieco Dixon na quantificação da gordura hepática em comparação com a espectroscopia por ressonância magnética (ERM), em exames de RM 3.0-T. Materiais e Métodos: Cinquenta e cinco participantes adultos sem doença hepática conhecida foram submetidos a RM 3.0-T para determinação da fração de gordura hepática, usando duas técnicas: multieco Dixon (em ROI desenhada manualmente e em segmentação automatizada para todo o parênquima hepático) e ERM. A precisão diagnóstica e o valor de corte para multieco Dixon foram determinados usando a ERM como padrão de referência. Resultados: A fração de gordura média usando multieco Dixon na ROI desenhada manualmente e na segmentação automatizada do fígado inteiro foi 5,2 ± 5,8% e 6,6 ± 5,2%, respectivamente. A fração de gordura hepática média usando ERM foi 5,7 ± 6,4%. Correlação positiva muito alta e forte concordância foram observadas entre ERM e multieco Dixon, tanto para ROI (r = 0,988, r2 = 0,978, p < 0,001) quanto para todo o parênquima hepático (r = 0,960, r2 = 0,922, p < 0,001). Correlação positiva moderada foi observada entre a fração de gordura hepática e o índice de massa corpórea dos participantes usando ambas as técnicas de estimativa de gordura. Conclusão: Multieco Dixon demonstrou correlação positiva muito alta e concordância com a ERM (muitas vezes considerada padrão de referência não invasivo) para quantificação de gordura hepática. Uma vez que o multieco Dixon está mais prontamente disponível do que a ERM, pode ser usado como uma ferramenta rápida para a quantificação da gordura hepática, especialmente na distribuição não homogênea da gordura.

Structural and functional characterization of peste des petits ruminants virus coded hemagglutinin protein using various in-silico approaches.

Peste des petits ruminants (PPR), a disease of socioeconomic importance has been a serious threat to small ruminants. The causative agent of this disease is PPR virus (PPRV) which belongs to the genus Morbillivirus. Hemagglutinin (H) is a PPRV coded transmembrane protein embedded in the viral envelope and plays a vital role in mediating the entry of virion particle into the cell. The infected host mounts an effective humoral response against H protein which is important for host to overcome the infection. In the present study, we have investigated structural, physiological and functional properties of hemagglutinin protein using various computational tools. The sequence analysis and structure prediction analysis show that hemagglutinin protein comprises of beta sheets as the predominant secondary structure, and may lack neuraminidase activity. PPRV-H consists of several important domains and motifs that form an essential scaffold which impart various critical roles to the protein. Comparative modeling predicted the protein to exist as a homo-tetramer that binds to its cognate cellular receptors. Certain amino acid substitutions identified by multiple sequence alignment were found to alter the predicted structure of the protein. PPRV-H through its predicted interaction with TLR-2 molecule may drive the expression of CD150 which could further propagate the virus into the host. Together, our study provides new insights into PPRV-H protein structure and its predicted functions.

Successful Treatment of Rituximab-Induced Crohn's Disease With Ustekinumab.

Autoimmune optic papillitis is a rare disorder that causes progressive visual loss, often treated with rituximab (RTX). However, its use is not without risks. Here, we present a 51-year-old man who experienced vision loss because of autoimmune optic papillitis, which was well-controlled with RTX. Four years later, the patient developed abdominal pain and diarrhea and was found to have RTX-induced Crohn's disease (CD). The patient failed treatment with azathioprine, but was subsequently able to achieve clinical and endoscopic remission of his CD with ustekinumab, while continuing RTX therapy for autoimmune optic papillitis. This case report describes the efficacy of the anti-interleukin 12/23 monoclonal antibody in inducing remission of RTX-induced CD.

Comparative evaluation of thermal impact of 980nm diode laser on soft tissue using irrigation and non-irrigation systems: A histomorphometric study.

Background: Diode laser is one of the most captivating technologies in dental practice. In periodontics, when used at appropriate settings, it possesses the best properties for selective surgical and nonsurgical procedures such as subgingival calculus removal without a thermal change of the root surface, and also provides tissue surface sterilization. However, lasers always produce a certain amount of thermal damage to the soft tissues. Therefore, this study aimed to comparatively evaluate the thermal impact of 980-nm diode laser incisions, when used with irrigation versus nonirrigation systems. Materials and Methods: The study was conducted on 24 gingival tissue samples obtained from the goat's mandible and maxilla. The samples were divided into two groups of 12 samples each, and laser incisions were given in 4 power settings, using 980-nm diode laser in super short pulse mode, with and without saline irrigation. Martius Scarlet Blue staining technique was used to prepare the histological slides. Then, slides were examined under a research microscope (Olympus CX 21), and the pictures of the slides were taken by mounting the camera onto the microscope mobile mount. The microscopic images hence obtained were analyzed for the depth and width of the incisions, area of carbonization, necrosis, and reversible damage, using the Digimizer image analysis software. Results: The results of this study demonstrated that the mean incision depth was higher (592.49 ± 180.97, P < 0.05), with less carbonization (25.52 ± 29.21, P = 0.00) and less necrosis (311.63 ± 156.441, P < 0.05) in the laser incisions with irrigation, as compared to the laser incisions given without irrigation system. Conclusion: Within the limitations of this study, it can be concluded that using an irrigation system causes less collateral damage while maintaining the incising efficiency of the diode laser. Further studies with a higher sample size, controlled irrigation systems, and incision techniques are needed to evaluate the efficiency of diode lasers for the clinical explanation of the results.

Multiple sexually transmitted infections as a presenting feature of human immunodeficiency virus/AIDS.

A 45-year-old married male presented with nonhealing, painless ulcers with purulent discharge over genitals for 3 months. He had molluscum contagiosum over genitalia and forehead. A tissue smear suggested a diagnosis of donovanosis. Biopsy suggested diagnosis of molluscum contagiosum and serology was positive for human immunodeficiency virus 1 and herpes simplex 2. The patient was started on acyclovir and doxycycline. Antiretroviral therapy was initiated. The patient responded slowly over a period of 8 weeks. Immunocompromised patients having nonhealing genital ulcers must be subjected to tissue smear to pick up the diagnosis of granuloma inguinale.

Predictive Validity of Anesthesiologists' Quality of Clinical Supervision and Nurse Anesthetists' Work Habits Assessed by Their Associations With Operating Room Times.

BACKGROUND: At all Joint Commission-accredited hospitals, the anesthesia department chair must report quantitative assessments of anesthesiologists' and nurse anesthetists' (CRNAs') clinical performance at least annually. Most metrics lack evidence of usefulness, cost-effectiveness, reliability, or validity. Earlier studies showed that anesthesiologists' clinical supervision quality and CRNAs' work habits have content, convergent, discriminant, and construct validity. We evaluated predictive validity by testing for (expected) small but statistically significant associations between higher quality of supervision (work habits) and reduced probabilities of cases taking longer than estimated. METHODS: Supervision quality of each anesthesiologist was evaluated daily by assigned trainees using the 9-item de Oliveira Filho scale. The work habits of each CRNA were evaluated daily by assigned anesthesiologists using a 6-item scale. Both are scored binary, 1 if all items are rated the maximum, 0 otherwise. From 40,718 supervision evaluations and 53,722 work habit evaluations over 8 fiscal years, 16 mixed-effects logistic regression models were estimated, with raters as fixed effects and ratees (anesthesiologists or CRNAs) as random effects. Empirical Bayes means in the logit scale were obtained for 561 anesthesiologist-years and 605 CRNA-years. The binary-dependent variable was whether the case took longer than estimated from the historical mean time for combinations of scheduled procedures and surgeons. From 264,060 cases, 8 mixed-effects logistic regression models were fitted, 1 per fiscal year, using ratees as random effects. Predictive validity was tested by pairing the 8 one-year analyses of clinical supervision, and the 8 one-year analyses of work habits, by ratee, with the 8 one-year analyses of whether OR time was longer than estimated. Bivariate errors in variable linear least squares linear regressions minimized total variances. RESULTS: Among anesthesiologists, 8.2% (46/561) had below-average supervision quality, and 17.7% (99/561), above-average. Among CRNAs, 6.3% (38/605) had below-average work habits, and 10.9% (66/605) above-average. Increases in the logits of the quality of clinical supervision were associated with decreases in the logits of the probabilities of cases taking longer than estimated, unitless slope = -0.0361 (SE, 0.0053), P < .00001. Increases in the logits of CRNAs' work habits were associated with decreases in the logits of probabilities of cases taking longer than estimated, slope = -0.0238 (SE, 0.0054), P < .00001. CONCLUSIONS: Predictive validity was confirmed, providing further evidence for using supervision and work habits scales for ongoing professional practice evaluations. Specifically, OR times were briefer when anesthesiologists supervised residents more closely, and when CRNAs had better work habits.

Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer.

OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.